The structural performance of reinforced concrete relies heavily on the bond between reinforcement and concrete. In nonlinear finite element analyses, bond is either modelled by merged, also called perfect bond, or coincident with slip, also called bond-slip, approaches. Here, the performance of these two approaches for the modelling of failure of reinforced concrete was investigated using a damage-plasticity constitutive model in LS-DYNA. Firstly, the influence of element size on the response of tension-stiffening analyses with the two modelling approaches was investigated. Then, the results of the two approaches were compared for plain and fibre reinforced tension stiffening and a drop weight impact test. It was shown that only the coincident with slip approach provided mesh insensitive results. However, both approaches were capable of reproducing the overall response of the experiments in the form of load and displacements satisfactorily for the meshes used.

In a concrete beam initially crack is generated at the tension side under the effect of flexure, shear and torsional loadings. Accordingly, these weak concrete members require repair and/or strengthening to increase or restore their internal load capacity. In the current experimental and numerical investigations on concrete beam having different width to depth ratio of notch on its ultimate flexural load under one-point loading was considered. Further, the flexural behavior performance of notch concrete beam repaired with the three repair materials cement mortar, bacterial mortar and adhesive was also examined. Consequently, a comparative study is imple-mented between the experimental and numerical results. Concrete Damage plasticity (CDP) model was used for finite element numerical analysis of beam. The differences in numerical and experimental measured results ranges from 0.65 - 22.20 % for the ultimate load carrying capacity. As the notch size increases the ultimate load carrying capacity of beam was reduced. Addition-ally, linear regression model is used to predict the ultimate load values at an interval of 5 mm notch width up to maximum width of notch 100 mm. It can be observed that the ultimate load capacity for repaired beam is increased as compared to the notch beam for all the three repairing materials under consideration. The maximum ultimate load was increased in case of notch beam repaired using adhesive. As compared to the cement mortar the performance of the bacterial mortar in terms of the ultimate load was more. The bacterial mortar is found more sustainable and more durable as a repair material for the concrete structures.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

The rise in both the frequency of natural disasters and the ubiquity of artificial intelligence has led to novel applications of new technologies in improving disaster response processes, such as the labor-intensive assessment of disaster damages. Assessment of residential and commercial structure damages, a precursory step to government agencies being able to provide most of their financial assistance, has benefited from aerial and satellite imagery-based computer vision models; however, limitations of using such imagery include the ground structures being obscured by clouds or smoke, as well as the lack of resolution to distinguish individual structures from others. Using a different data source, we propose a damage severity classification model using ground-level imagery, focusing on residential structures damaged by wildfires. This classifier, a Vision Transformer (ViT) model trained on over 18,000 professionally labeled images of damaged homes from the 2020-2022 California wildfires, has achieved an accuracy score of over 95%. Further, we have open sourced the training dataset–the first of its kind and scale–as well as built a publicly available web application prototype, which we demoed to and received feedback from disaster response officials, both of which further contribute to the broader literature beyond the proposed model.

Lineage plasticity, the switching of cells from one lineage to another has been recognized to be a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of Epithelial-Mesenchymal Transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that “core” mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a “core” mechanism is the initiation of behavioral shifts through the modulation of a conserved “social decision-making network”, along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was activated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provided insights into phenotype switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

Constitutive models for plastic deformation of metals are typically based on flow rules determining the transition from elastic to plastic response of a material as function of the applied mechanical load. These flow rules are commonly formulated as a yield function, based on the equivalent stress and the yield strength of the material, and its derivatives. In this work, a novel mathematical formulation is developed that allows the efficient use of machine learning algorithms describing the elastic-plastic deformation of a solid under arbitrary mechanical loads and that can replace the standard yield functions with more flexible algorithms. By exploiting basic physical principles of elastic-plastic deformation, the dimensionality of the problem is reduced without loss of generality. The data-oriented approach inherently offers a great flexibility to handle different kinds of material anisotropy without the need for explicitly calculating a large number of model parameters. The applicability of this formulation in finite element analysis is demonstrated, and the results are compared to formulations based on Hill-like anisotropic plasticity as reference model. In future applications, the machine learning algorithm can be trained by hybrid experimental and numerical data, as for example obtained from fundamental micromechanical simulations based on crystal plasticity models. In this way, data-oriented constitutive modeling will also provide a new way to homogenize numerical results in a scale-bridging approach.

Eyes are quintessential complex traits and our understanding of their evolution guides models of trait evolution in general. A long-standing account of eye evolution argues natural selection favors morphological variations that allow increased functionality for sensing light (Darwin 1859; v. Salvini-Plawen and Mayr 1977; Nilsson and Pelger 1994; Nilsson 2013). While certainly true in part, this focus on visual performance does not entirely explain why diffuse photosensitivity persists even after eyes evolve, or why eyes evolved many times, each time using similar building blocks. Here we briefly review a vast literature indicating most genetic components of eyes historically responded to stress caused directly by light, including UV damage of DNA, oxidative stress, and production of aldehydes. We propose light-induced stress had a direct and prominent role in the evolution of eyes by bringing together genes to repair and prevent damage from light-stress, both before and during the evolution of eyes themselves. Stress-repair and stress-prevention genes were perhaps originally deployed as plastic responses to light and/or as beneficial mutations genetically driving expression where light was prominent. These stress-response genes sense, shield, and refract light but only as reactions to ongoing light stress. Once under regulatory-genetic control, they could be expressed before light stress appeared, evolve as a module, and be influenced by natural selection to increase functionality for sensing light, ultimately leading to complex eyes and behaviors. Recognizing the potentially prominent role of stress in eye evolution invites discussions of plasticity and assimilation and provides a hypothesis for why similar genes are repeatedly used in convergent eyes. Broadening the drivers of eye evolution encourages consideration of multi-faceted mechanisms of plasticity/assimilation and mutation/selection for complex novelties and innovations in general.

The loss of integrity and adverse effect on mechanical properties can be concluded as attributing miro/macro-mechanics damage in structures, especially in composite structures. Damage as a progressive degradation of material continuity in engineering predictions for any aspects of initiation and propagation requires to be identified by a trustworthy mechanism to guarantee the safety of structures. Besides the materials design, structural integrity and health are usually prone to be monitored clearly. One of the most powerful methods for the detection of damage is machine learning (ML). This paper presents the state of the art of ML methods and their applications in structural damage and prediction. Popular ML methods are identified and the performance and future trends are discussed.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, high-dose Cy exposure can cause nerve injury with symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor ability. Moreover, it was found that medium- and high-dose Cy exposure can cause disordered energy metabolism in hippocampal cells and an abnormal release of the neurotransmitter Glu. Second, pathological brain sections showed that the middle and high doses of Cy caused deformation, reduction and disorder of hippocampal pyramidal cells, a decrease in the number of Nissl bodies, pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, with the increase in exposure dose, the morphological changes in hippocampal synapses were more obvious, including blurred synaptic spaces, decreased synaptic vesicles and a decreased number of synapses. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus, and the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators, inflammatory factors, synaptic plasticity factors and apoptosis factors, suggesting that Cy may cause nerve damage in rats and has a close relationship with A2AR.

D-Serine, a co-agonist of NMDA receptors has sparked a contentious debate within the scientific community regarding its status as a gliotransmitter or a neurotransmitter. This comprehensive review delves into the heart of this debate, offering a meticulous analysis of the existing evidence from various research methodologies. Immunostaining studies and cell-selective mutations provide compelling support for D-serine's neuronal origin, bolstering the serine shuttle model. In contrast, the gliotransmission hypothesis, proposing astrocytic synthesis and release, faces critical scrutiny as inconsistencies in supporting data emerge. In vivo microdialysis experiments unveil a neuronal contribution to D-serine release and its profound impact on synaptic plasticity, further strengthening the case for neuronal dominance. Counterarguments in favor of astrocytic D-serine release are systematically dissected, revealing inherent limitations and ambiguities. Collectively, the evidence corroborates D-serine's neuronal source and discounts the astrocytic hypothesis. This review underscores the need for scientific rigor when evaluating contentious topics and affirms the simplicity of the neuronal explanation, aligning D-serine with the serine shuttle model, thus advancing our comprehension of its pivotal role in synaptic function and cognitive processes. As the debate continues to evolve, this exploration encourages ongoing research to unravel the intricate mechanisms governing D-serine neurotransmission.

Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.

A paper recently published by eLife on forebrain cortical synaptic plasticity reports that retinoic acid (RA) alters synaptopodin-dependent metaplasticity in mouse dentate granule cells (Lenz et al., 2021). RA is the active form of vitamin A that functions as a ligand for nuclear RA receptors that directly bind genomic control regions to regulate gene expression (Chambon, 1996; Ghyselinck and Duester, 2019). However, some studies have suggested that RA may have nongenomic effects outside of the nucleus, particularly with regard to synaptic plasticity (Aoto et al., 2008; Zhang et al., 2018). The current results reported by Lenz et al. demonstrate that treatment with pharmacological levels of RA can alter synaptic plasticity which may be useful to treat neurological diseases (Lenz et al., 2021). However, the results reported here and those reported by others have not shown that endogenous RA is normally required for synaptic plasticity (or any other nongenomic effect) as there are no reports of genetic loss-of-function studies that remove endogenous RA in adult brain. The implication is that pharmacological levels of RA result in nongenomic effects, some of which may be helpful to treat certain diseases but in other cases this may cause unwanted side-effects.

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes to a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure under the above described constraints.

In recent years, many molecular and environmental factors have been studied to understand how synaptic plasticity is modulated. Sleep, as an evolutionary conserved biological function, has shown to be a critical player for the consolidation and filtering of synaptic circuitry underlying memory traces. Although sleep disturbances do not alter normal memory consolidation, they may reflect fundamental circuit malfunctions that can play a significant role in exacerbating diseases, such as autism and Alzheimer’s disease. Very recently, scientists sought to answer part of this enigma and they identified p75 neurotrophic receptor (p75NTR) as a critical player in mediating impairments in hippocampal-dependent associative plasticity upon sleep deprivation. This paper will review the role of the p75NTR, critically discuss the impact and implications of this research as the bridge for sleep research and neurological diseases.

In this work, plastic deformation was locally introduced at room temperature by nanoindentation on a γ-TiAl based alloy. Comprehensive analyzes of microstructures were performed before and after deformation. In particular, the Burgers vectors, the line directions and the mechanical twinning systems were studied via accurate electron channeling contrast imaging. Accommodation of the deformation are reported and a scenario is proposed. All features help to explain the poor ductility of the TiAl based alloys at room temperature.

This paper constructs a model of climate-related damage for small island developing states (SIDS). We focus on the loss of private productive capital stocks through extreme climate events. In contrast to most economic analyses of climate impacts, which assume temperature-dependent damage functions, we draw on the engineering literature to allow for a greater or lesser degree of anticipation of climate change when designing capital stocks and balancing current adaptation expenditure against future loss & damage. We apply the model to tropical storm damage in the small island developing state of Barbados and show how anticipatory behavior changes the damage to infrastructure for the same degree of climate change. Thus, in the model, damage depends on behavior as well as climate variables.

In this paper we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the Free Energy Principle, we can emphasize the role of fostering resource renewal, harmonious system-entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability, both in an agent and in collectives. We start by connecting Active Inference with well-being, building on exsiting work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent, and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

Plant responses to different light and water availability are variable among species and their re-spective phenotypic plasticity, and the combination between these two abiotic factors can alleviate or intensify stressful effects. This study aimed to evaluate the impacts of exposure time of Cedrela fissilis Vell. seedlings to different water and light availability and the interaction of these factors. Seedlings were submitted to combinations of three shading levels – SH (0, 30 and 70%) and three water regimes based on the water holding capacity (WHC) in the substrate, constituting nine cul-tivation conditions: T1 – 0% SH + 40% WHC; T2 – 0% SH + 70% WHC; T3 – 0% SH + 100% WHC; T4 – 30% SH + 40% WHC; T5 – 30% SH + 70% WHC; T6 – 30% SH and 100% WHC; T7 – 70% SH + 40% WHC; T8 – 70% SH +70% WHC; T9 – 70% SH + 100% WHC. C. fissilis seedlings respond to water deficit, here represented by 40% WHC, regardless of exposure time, and when cultivated in full sun, the stressful effects were enhanced, acting in a synergistic manner. The condition that provided better gas exchange performance and greater total dry mass accumulation for C. fissilis seedlings was 30% shading combined with 100% WHC. C. fissilis seedlings have physiological plasticity and resilience to survive under different water and light conditions.

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF, BDNF or NT-3 protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT. In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review we summarize these evidences and discuss them in the context of other motor systems.

A rehabilitation technique for asphalt pavements with geosynthetic is the application of impregnated nonwoven geotextiles between deteriorated and new asphalt overlays. The performance investigation of impregnated geotextiles proves that they are enhancing in mechanical and hydraulic properties. Although, the installation process may cause severe impacts on these materials’ performance. During the installation, the geotextile suffers damage due to the traffic of high load vehicles, as compactors and pavers, and the friction with granular materials found under its layer or poured above it. This paper aims to investigate how the damage caused by granular materials on nonwoven geotextiles impregnated with different asphalt emulsions effect on their strength resistance and permittivity. From two types of nonwoven geotextiles: polypropylene and polyethylene terephthalate, the comparison uses geotextiles in three conditions: not impregnated, impregnated with asphalt emulsion of rapid setting, and impregnated with asphalt emulsion changed by an elastomeric polymer. Part of the samples followed the damage according to ISO 10722 procedure, placed between three different scenarios of granular materials, applying gravel, sand, and clay. After the damage process, the samples were submitted to mechanical and hydraulic properties evaluations.

Fibre-reinforced composite structures under complex loads exhibit gradual damage behaviour with a degradation of effective mechanical properties and change of their structural dynamic behaviour. Damage manifests itself as spatial increase of inter-fibre failure and delamination-growth, resulting in local changes of stiffness. These changes affect not only the residual strengths but more importantly the structural dynamic behaviour. In case of composite rotors, this can lead to catastrophic failure if an eigenfrequency coincides with the rotational speed. The description and analysis of the gradual damage behaviour of composite rotors therefore provides the fundamentals for a better understanding of unpredicted structural phenomena. The gradual damage behaviour on the example of composite rotors and the resulting damage-dependent dynamic behaviour is experimentally investigated under propagating damage for combined out-of-plane and in-plane loads. A novel observation is reported, where monotonic increase of damage results in non-monotonic frequency shift of significant amount of eigenfrequencies.

The focus of recent research shifts towards complex ‘whole organism’ responses (i.e., in multiple functional traits) in adaptation to or to defend against stressors under complex environmental conditions. This increasing complexity is challenging to analyse and demands sophisticated tools to drive meaningful conclusions from those data. Trait-based regression models, multivariate analyses, like principal component analyses, and plasticity indices can be used to tackle challenges with those complex investigations. But those methods have substantial limitations, like the need for high sample size, multi-dimensionality of results or the need for trait coordination in high-dimensional space, or the calculation on the population level, which might buffer or cover the de facto occurring individual effects. To improve and simplify studies on ‘whole organism’ responses, analyses, and their interpretation, we developed the Index for Adaptive Responses. This straightforward framework can unite all traits of an organism in one number. A newly developed transformation method, included in this framework, comprises a normalisation and standardisation to a baseline or control without changing the data or variance structure of the original data. We assessed the performance and accuracy of the framework with an application in an extensive predator-prey case study, with simulations and application examples using literature data. We show that the Index for Adaptive Responses respects adaptations as well as maladaptations and outperforms established approaches. The framework is robust against outliers and non-gaussian distribution. We further show that the qualitative prediction of the adaptiveness of included traits is highly accurate, even under challenging conditions, e.g., low replicate numbers. Functions and algorithms of the framework are provided with an R package but can easily be translated into other programming languages. The Index for Adaptive Responses will simplify future research on complex adaptive responses and improves our understanding of these responses’ ecological as well as evolutionary implications.

This contribution was devoted to unveil the strain rate sensitivity (SRS) of G18NiCrMo3-6 cast steel in tension/compression asymmetry. For that purpose, detailed mechanical characterization tests were conducted providing a process window covering quasi-static and medium strain rate regimes (0.001, 0.1, 10 [ s¯¹]) in tension and compression states. By means of this experimental ef-fort, the SRS of the material could be extracted by a function of strain and strain rate which ena-bling to create a mathematical expression to easily be implemented as a state variable for constitu-tive material modeling. Finally, a pressure and rate dependent constitutive material model on the basis of Cocks'89 yield locus definition was created by a subroutine (UMAT) file and the material parameters were verified with respect to the experimental data. The UMAT file also takes into account the tension/compression asymmetry in yielding to handle the effect of porous media plas-ticity concept. The predictions of the proposed material model are quite in line with the experi-mental outputs.

Defining the best conditions for the initial development of native species is one of the significant challenges to forest production. Therefore, this study aimed to evaluate andiroba's physiological behavior and growth (Carapa guianensis Aubl.) seedlings at different shading levels. In a nursery seedling, C. guianensis seedlings grew on 0, 30, 50, and 70% shading, obtained with polyethylene screens. We measured at six plants per treatment. For the physiological data we measurement four times the total chlorophyll content, chlorophyll a/b ratio, maximum photochemical efficiency of photosystem II (Fv/Fm), maximum potential photosynthesis (A), stomatal conductance (gs), transpiration (E), intrinsic water use efficiency (WUEi), and carbon use efficiency (CUE), besides the growth parameters. While for growth rates parameters we developed six evaluation for as leaf area ratio (LAF), relative growth rates (RGR), and net assimilation rate (NAR). Chlorophyll content and Fv/Fm were inversely proportional to the light intensity. The other physiological and growth parameters showed better behavior in shaded environments, emphasizing the 50% treatment, with no significant difference between the 30% shading treatment. Therefore, the C. guianensis seedlings present growth plasticity under different shading levels, and we recommended producing seedlings at 50 or 30% shading.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be explored. A diverse array of targeting agents is currently under evaluation in pre-clinical and clinical studies with promising results in suppressing or reversing the neuroendocrine phenotype and inhibiting tumor growth and metastasis. This new knowledge has the potential to contribute to development of novel therapeutic approaches that may enhance clinical management and prognosis of this lethal disease.

Doped copper overpacks are planned to be utilized in the spent nuclear fuel repositories in Finland and in Sweden. The assessment of long-term integrity of the material is a matter of importance. Grain structure variations, segregation and any possible manufacturing defects in microstructure are relevant in terms of susceptibility to creep and damage from the loading evolution imposed by its operating environment. This work focuses on studying the microstructure level length-scale dependent deformation behavior of the material, of particular significance with respect to accumulation of plasticity over the extensive operational period of the overpacks. Reduced micromorphic crystal plasticity model, which is similar to strain gradient models, is used in this investigation. Firstly, the model’s size dependent plasticity effects are evaluated. Secondly, different microstructural aggregates presenting overpack sections are analyzed. Grain size dependent hardening responses, i.e., Hall-Petch like behavior, can be achieved with the enhanced hardening associated with the micromorphic model at polycrystalline level. It was found that the nominally large grain size in the base material of the overpack shows lower strain hardening potential than the fine grained region of the welded microstructure with stronger strain gradient related hardening effects. Size dependent regularization of strain localization networks is indicated as a desired characteristics of the model. The findings can be utilized to provide an improved basis for modeling the viscoplastic deformation behavior of the studied copper alloy and assess the microstructural origins of any integrity concerns explicitly by way of full field modeling.

This paper describes a new generation of computational intelligence founded on the ancient idea of compassion called Artificial Compassion. The creation of Artificial Compassion is the result of two coinciding historical developments. The first is the increasing discoveries of human sciences in new fields like neuroendocrinology and psychoneuroimmunology. This provides the spark for Artificial Compassion. For example, we once thought with certainty that our brain is fixed for life but neuropsychology and a device called the fMRI have shown it is “plastic”. It changes constantly throughout our lives in response to our experiences. Remarkably, we also now know it is changed for the better through positive emotions like compassion, kindness and happiness. So, too, are the immune, endocrine, genetic, cardio and neural systems influenced and changed by our emotional experiences. This new perspective on emotions and plasticity validates much of ancient wisdom in medical systems outside the west. Long held assumptions about emotion are unsuitable for humanity. The second development is ‘machine rub off’. We are in symbiotic relation with our devices today and we are plastic. We are changed by our interactions but many people have computer rage. We need Artificial Compassion to replace computer rage with positive plasticity.

In order to study the effect of TiB2 particles on the mechanical properties of TiB2/6061Al composites, a series of TiB2/6061Al 3D representative volume element (RVE) were established based on SEM photos. This model took into account the ductile damage of the matrix and the traction separation behavior of the interface, and the linear damage evolution law was introduced to characterize the stiffness degradation behavior of the matrix elements. The mixed boundary conditions were used for RVE tensile experiments, and the accuracy of the predicted result was verified by the agreement of the experimental stress-strain curve. Results show that the addition of TiB2 particles can effectively promote the load-bearing capacity of the composite, but elongation is reduced. With the weight fraction of TiB2 increasing from 2.5% to 12.5%, the elastic modulus, yield strength, and tensile strength are increased by 8%, 10.37%, and 11.55% respectively, while the elongation decreased by 10%. The clustering rate of the TiB2 particles is also an important factor affecting the toughness of the composites. With the increase in the clustering rate of TiB2 particles from 20% to 80%, the load-bearing capacity of the composites is not improved, and the elongation of the composites is reduced by 8%. Moreover, the high strain region provides a fast expansion path for crack propagation and the particle spacing is a crucial factor that affects the stress field.

High costs for the repair of concrete structures can be prevented if damage at an early stage of degradation is detected and precautionary maintenance measures are applied. To this end, we use numerical wave propagation simulations to identify simulated damage in concrete using convolutional neural networks (CNN). Damage in concrete subjected to compression is modeled at the mesoscale using the discrete element method. Ultrasonic wave propagation simulation on the damaged concrete specimens are performed using the rotated staggered finite-difference grid method. The simulated ultrasonic signals are used to train a CNN based classifier capable of classifying three different damage stages (microcrack initiation, microcrack growth and microcrack coalescence leading to macrocracks). The performance of the classifier is improved by refining the dataset via an analysis of the averaged envelope of the signal. The classifier using the refined dataset has an overall accuracy of 90%.

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

The main consequence of radiation damage on a Silicon-Photomultiplier (SiPM) is a significant increase in the dark current. If the SiPM is not adequately cooled, the power dissipation causes it to heat up, which in turn affects its performance based on the temperature. In order to investigate this heating effect, experiments were carried out using a KETEK SiPM glued on an Al2O3 substrate, as well as HPK SiPMs that were either glued onto an Al2O3 substrate or a flexible PCB. The assemblies were connected either directly to a temperature-controlled chuck on a probe station or through layers of materials with well-defined thermal resistance. A DC-mode LED was used to illuminate the SiPM, and the resulting SiPM current was measured to determine the steady-state temperature. This temperature depended on the power dissipated in the multiplication region of the SiPM and the thermal resistance. This information can be utilized to adjust the SiPMs working point, taking into account the effects of self-heating. Similarly, this approach can be applied to packaged SiPMs that have an unknown thermal contact to a heat sink.

Recently on the November 4, 2022 at 03:00 PM, a M_ww 5.6 earthquake struck Cianjur district of West Java province, Indonesia. To our best knowledge, an earthquake will cause a massive damage to the manmade infrastructure and this responsible for a massive casualty. A building damage is affected by various determinant factors. One of important factors is the geological bedrock variations. Here this research aiming to elaborate the associations of geological bedrocks in Cianjur district with residential building damages caused by recent earthquakes. The results confirm that majority of building damages account for 54.67% of the total building was associated with quaternary volcanic bedrocks. The second massive building damages were observed for Andesitic Dacitic volcanic rocks accounted for 32.07%. To conclude, elaborations of geological bedrock-building damage will contribute to the better planning in the future that can reduce the damages in the urban settings.

Samarinda City is one of the most attractive cities in Borneo Island (Indonesia) and also as a capital city of EastBorneo Province. The expansion of urban areas becomes essential due to rapid population and housing demand. Base on the statistical report, the annual population growth rate is 0.018% from the year 2016-2017 with a total population of 843446 inhabitants. Many natural disasters occur in some areas in this city, especially flooding. This natural disaster occurs almost every year, many people suffered and forced to evacuate. In 2018 there is 3 flood event with 28311 people was suffered and evacuated, and 5170 houses were flooded [1]. During the flood event, it was very possible to gain damages to their property and make traffic stuck. One common way to reducing the damages is using Early Warning Systems (EWS). Early warning is a major element for disaster risk reduction, including damages. To prevent and mitigate the impact of a disaster, many countries had taken action to build various methods of a public warning system. An effective early warning system focused on people-centered and comprises the following element, such as risk knowledge, technical monitoring and service, communication and dissemination of warnings, and community response capability [2]. Related to the existing condition which Samarinda is a Muslim-dominated city and obviously has a lot of a number of mosques. This is a good potency to develop an early warning system because every mosque has a loudspeaker for echoing Adzan (Muslim prayer-calling). With this existing condition, the loudspeaker can be utilized as a flood outdoor-voice warning announcer. The aim of this study is to briefly introduce the strategy of dissemination early warning by utilizing mosques. The hope of early warning dissemination is giving enough time to the people to evacuate their property to reduce damages and possibly to giving information to avoiding traffic stuck (in a certain location)due to flooding. The results of this study can be used as input for decision-makers to develop effective flood management strategies and policies, especially in the case of an early warning system where not well-developed in Samarinda.

Historic sites are important components of every city's cultural history because they preserve rich historical knowledge and distinctive values passed down from previous generations to the present. Due to the progress of urbanization and modernization, many historic sites face pressure from damage and transformation. In this paper, a method for assessing cultural heritage damage was developed to measure the extent of spatial damage in historic sites. Using sample data obtained in Xiyang, Qixian, and Xiaoyi, all historic cities in Shanxi Province, Mainland China, and combined weights were estimated using the Delphi technique and the CRITIC weight method. Following this, the Spatial Damage Degree Model (SDDM) based on K-means cluster analysis and K-nearest neighbor (KNN) classification was developed. The findings show that the model efficiently solves the problem of assessing spatial damage levels in historic sites. Through multiple linear regression analysis, it was shown that the damage to historic sites was predominantly caused by three factors: natural erosion, construction damage, and planning and policy. SDDM was used to calculate the spatial damage levels of historic sites, allowing conservators to fully comprehend the features and concerns related to historic sites. As a result, more scientific and rational preservation approaches may be developed, improving the efficiency of historic site restoration and conservation and encouraging the sustainable development of urban and rural heritage.

The therapeutic effects of volatile anesthetics on mental diseases, particularly schizophrenia, have gained considerable interest. Although isoflurane is a commonly used volatile anesthetic, there’s no more evidence that it could work on treating schizophrenia. Here, we discovered that inhaling isoflurane at low concentrations might reverse the behavioral phenotypes of schizophrenia caused by MK801, such as hyperlocomotion, pre-pulse inhibition impairment, and working memory loss. Isoflurane also helped recovering adult neurogenesis and synaptic plasticity impairments in the dentate gyrus (DG) induced by MK801. To better understand the mechanism, we discovered that isoflurane could reverse the reduction of parvalbumin (PV)-positive GABAergic interneuron (PVI) number and the aberration of NRG1-ErbB4 signaling in the DG; however, isoflurane could not reverse the schizophrenia-related phenotypes caused by PVI ablation, indicating that PVI are necessary for the therapeutic effect of isoflurane. Interestingly, isoflurane could reverse phenotypes caused by blocking PVIs GABA release in the DG, indicating the therapeutic impact is independent of PVI GABA release. Our research revealed that isoflurane might be used to treat schizophrenia, possibly through PVI in the DG.

For the numerical simulation of components made of short fiber-reinforced composites the correct prediction of the deformation including the elastic and plastic behavior and its spatial distribution is essential. When using purely deterministic modeling approaches the information of the probabilistic microstructure is not included in the simulation process. One possible approach for the integration of stochastic information is the use of random fields. In this study numerical simulations of tensile test specimens are conducted utilizing a finite deformation elastic-ideal plastic material model. A selection of the material parameters covering the elastic and plastic domain are represented by cross-correlated second-order Gaussian random fields to incorporate the probabilistic nature of the material parameters. To validate the modeling approach tensile tests until failure are carried out experimentally, that confirm the assumption of spatially distributed material behavior in both the elastic and plastic domain. Since the correlation lengths of the random fields cannot be determined by pure analytic treatments, additionally numerical simulations are performed for different values of the correlation length. The numerical simulations endorse the influence of the correlation length on the overall behavior. For a correlation length of 5mm a good conformity with the experimental results is obtained. Therefore, it is concluded, that the presented modeling approach is suitable to predict the elastic and plastic deformation of a set of tensile test specimens made of short fiber-reinforced composite sufficiently.

Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

The theory of the origin of carcinomas suggests that neoplasias from epithelial tissues are the consequence of the reactivation of developmental programs. It proposes a model in which the epithelial cells undergo cellular transitions due to replicative senescence and inflammation towards a mesenchymal-undifferentiated phenotype with cancerous behavior. The conserved pattern of histological progression and the molecular biology of carcinomas is congruent with the view of cancer as a developmental disease. In support of the theory, the experimental literature regarding the molecular, cellular, and histopathological mechanisms associated with epithelial carcinogenesis were aligned according to the premises of the hypothesis. Thereby identified a generic process in the carcinogenesis of the breast, endometrium, prostate, colon, lung, pancreas, bladder, liver, and cervix. Then, is provided a methodology overview of modeling in systems biology derived from previous research testing the hypothesis. The results illustrate the value of the complex systems approach to recover behavior that cannot be inferred only by traditional methods. Specifically, the model suggests that the consistency in the cell types and the directionality of the observed cellular transitions during epithelial carcinogenesis arise from structural constraints in the molecular networks associated with the carcinomas. Overall, the results of the dynamical analysis agree with the premises of the hypothesis and provide an insightful perspective of the potential mechanisms underlying the cellular plasticity displayed during epithelial carcinogenesis. In an era of big data and yet few advances in the underlying causes of chronic diseases, the manuscript also aims to inspire molecular biologists to integrate existing empirical evidence with systems biology modeling in the pursuit of understanding.

In million years, under the pressure of natural selection, hominins acquired vocal learning, music, language, and intense cooperation, thanks to the efficacy of music in enhancing sociality. Thus, early in human evolution music became part of human life, a relevant activity, which required sophisticated perceptual and motor skills. It contributed to developing cultures and history, social bonding, and from the beginning of life strengthens the mother-baby relation while within the mother’s womb. Music existed in all known human cultures, although it varies in rhythmic and melodic complexity. It is art made of sounds capable of arousing emotions, evokes memories, engages multiple cognitive functions, and promotes attention, concentration, stimulates the imagination, creativity, and harmony of movement. Music and language share the same complex neural network. Music changes the chemistry of the brain activating the reward and prosocial systems, altruism, and allowing its use in therapy. This review explores "what" is music and illustrates the neural circuits that allow the production of music and language and those that transduce the sounds perceived by the ear, localize and archive them, allowing to recall them. Interestingly, songbirds share many commonalities with human music:, common neural pathways that shape vocal learning, and how they make sounds.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

Safety assessment of structures can be obtained employing limit design to overcome uncertainties concerning actual response due to inelastic constitutive behavior and more generally to non-linear structural response and loads’ random variability. The limit analysis is used for evaluating the safety of the structures directly starting from load level without any knowledge of the load history. In the paper, the lower bound calculation is proposed where a new strain-based approach is used that allowed describing the residual stress and displacement in terms of permanent strain. The strategy used the permanent strain as the effective parameters of the procedure so that it was possible to assess the ductility requirements for the complete load program developed till collapse or shakedown. The procedure is compared to experimental results obtained on aluminum beams in shakedown.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

The relative dislocation density of aluminum and copper samples is quantitatively measured using linear Resonant Ultrasound Spectroscopy (RUS). For each metallic group, four samples were prepared with different thermomechanical treatments in order to induce changes in their dislocation densities. The RUS results are compared with Nonlinear Resonant Ultrasound Spectroscopy (NRUS) as well as Second Harmonic Generation (SHG) measurements. NRUS has a higher sensitivity by a factor of two to six and SHG by 14% to 62%. The latter technique is, however, faster and simpler. As main a result we obtain a quantitative relation between the changes in the nonlinear parameters and the dislocation density variations, which in a first approximation is a linear relation between these differences. We also present a simple theoretical expression that explains the better sensitivity to dislocation content of the nonlinear parameters with respect to the linear ones. X-Ray diffraction measurements, although intrusive and less accurate, support the acoustics results.

Psoriasis is a multi-factorial immune-mediated disease that affects approximately 2% of the UK population and 2.5% worldwide. The condition can impact multiple organs, including the skin and joints. In moderate to severe cases, systemic and topical medications may not provide adequate relief, and as a result, biologic treatments are often administered as a monotherapy or in combination with other treatments. While biologic treatments are more effective than systemic and topical medications in treating psoriasis, patients require close supervision and monitoring while receiving this type of treatment. Liposomes are highly versatile and can be employed for therapy and research applications. They enhance drug retention at the site of administration, thereby reducing systemic side effects. Our study was the first to investigate the genotoxicity of secukinumab, an ideal biologic treatment for psoriasis (a human IgG1k antibody, anti-IL17A), in bulk and liposome nanoparticles on the lymphocytes of psoriasis patients compared to healthy individuals. We evaluated and com-pared the genotoxicity of secukinumab in bulk and liposomal form using the Comet and micronucleus assays. Both assays demonstrated that secukinumab in both forms did not ex-hibit genotoxicity and reduced DNA damage following treatment of the lymphocytes from healthy individuals and psoriatic patients with secukinumab bulk and liposomes format. Both concentrations of secukinumab used (2.1 and 2.8 µg/mL) effectively decreased H2O2-induced DNA damage in both groups to nearly the level of the negative control. Secukinumab bulk and liposome form significantly decreased H2O2-induced damage and efficiently attenuated its adverse effects both in the Comet (p<0.0001) and micronucleus assays (p<0.01). Overall, secukinumab in both forms exhibited protective and an-ti-genotoxic effects by demonstrating its potential to reduce DNA damage caused by oxida-tive stress and by not inducing any further damage in the lymphocytes of either healthy in-dividuals or patients.

InGaN-based red micro light-emitting diodes (µLEDs) of different sizes prepared in this work. The red GaN epilayers were grown on a 4-inch sapphire substrate through metal organic chemical vapor deposition (MOCVD). Etching, sidewall treatment, and p- and n- contact deposition was involved in the fabrication process. Initially, the etching process would cause undesirable damages to the GaN sidewalls, which leads to an increase in leakage current. Hence, we employed KOH wet treatment to rectify the defects on the sidewalls and conducted a comparative and systematic analysis on electrical as well as optical properties. We observed that the µLEDs with a size of 5µm exhibited substantial leakage current, which was effectively mitigated by the application of KOH wet treatment. In terms of optical performance, the arrays with KOH demonstrated improved Light Output Power (LOP). Additionally, while photoelectric performance exhibited a decline with increasing current density, the devices treated with KOH consistently outperformed their counterparts in terms of optoelectronic efficiency. It is noteworthy that the optimized devices displayed enhanced photoelectric characteristics without significantly altering their original peak wavelength and FWHM. Our findings point to the elimination of surface non-radiative recombination by KOH wet treatment, thereby enhancing the performance of small-sized red µLEDs which has significant potential in realizing full-color micro-displays in near-eye projection applications.

Despite being extremely potent against malignancies, cisplatin (CIS) has limited practical applicability due to its adverse effects such as testicular damage. Consequently, it becomes necessary to reduce its toxicity. In this study, cilostazol, a selective phosphodiesterase-3 inhibitor that is frequently used in the treatment of intermittent claudication, was examined for its ability to abrogate CIS-induces testicular toxicity and its ameliorative effect was compared with two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Ten groups of rats were included; Group (1): control, Groups (2-4): 5 mg/kg tadalafil or 75 mg/kg pentoxifylline or 20 mg/kg cilostazol respectively), Group (5):7 mg/kg CIS, Group (6&7): CIS + 5 mg/kg tadalafil or 75 mg/kg pentoxifylline, Group (8-10) CIS+ 5, 10 or 20 mg/kg cilostazol respectively. CIS treated rats showed a significant decrease in testicular function, serum testosterone and reduced glutathione levels, and significant elevation in malondialdehyde, total nitrite levels, tumor necrosis factor-alpha and nuclear factor-kappa β alongside caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary, Cilostazol in a dose-dependent manner showed potential protection against testicular toxicity, reversion of the disrupted testicular function and improvement of the histological alterations through rebalancing of oxidative stress, inflammatory and apoptotic biomarkers. In addition, cilostazol exerted more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, administrations of cilostazol might ameliorate cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathway, offering a promising treatment for cisplatin -intoxication in the testes.

Free-edge effect is one of the factors affecting the mechanical properties of three-dimensional woven composites under tensile load. However, current research is relatively poorly understood regarding the effect of free-edge on the stiffness and strength of the material. This paper aims at examining the influence of free-edge effect on the mechanical properties of 3D woven composites under tension through experimental and simulation mathods. The three-dimensional DIC technique is used to collect the full-field strains on the specimen surface during the test, and the stress-strain differences in different regions in the width direction are analyzed, and the overlap of the curves in each region is found to be high. Experimental studies are conducted on specimens of different widths (within the range of 15-20 mm), and the results indicate that the differences in mechanical properties of 3D woven composites under tension loading in this width range are not significant. A progressive damage finite element model is developed for calculation and compared with experimental results.

The coffee leaf miner Leucoptera coffeella (Guérin-Mèneville & Perrottet), is a key pest in coffee producing countries. During their development, the larvae feed on the palisade parenchyma of the leaves forming mines. As a result, the photosynthetic area of the plant decreases, affecting coffee production. Despite the severity of the damage caused by coffee leaf miner (CLM), morphological aspects of the larval development and the adult genitalia remain unknown. It is important to identify more susceptible targets to an efficient and narrow control by natural or synthetic approaches, relies on determining the larval instars. Equally important is the sexing of the adult, in experiments aiming efficient ways to control CLM, as the study of pheromone-based control methods. This work presents the first morphological description of the four larval instars and the adult genitalia of L. coffeella. In each larval instar, we measured the Mean ± SD (mm) of the cephalic capsules (1^st 0,14±0,03; 2^nd 0,25±0,04; 3^rd 0,32±0,03; 4^th 0,42±0,03) and observed the following morphological details: primary setae, prolegs, crochets and ecdysial line of the cephalic capsule. In the adults, we observed the sexual structures present in both genitalia: male - bulbus ejaculatorius, valva, anellus, gnathos and aedeagus and female - ovipositor, sclerite and corpus bursae. The dissection of the adult specimens confirmed that the external morphology corresponds to the correct sex attribution in CLM adults. These results may support innovative and improved control strategies for CLM Integrated Pest Management (IPM).

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localized mRNA translation is im-portant for the structural changes at synapses supporting brain plasticity consolidation. Sleep has been shown activate the translation mTOR pathway, via phosphorylation of 4E-BPs, during brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BPs phosphorylation at cortical and cerebellar synapses with Western Blot. Sleep significantly increased the conversion of 4E-BPs to its hyperphosphorylated form at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band dur-ing active exploration and in the theta to beta (4-30Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BPs hyperphosphorylation at synapses. Our results provide a link between EEG and mo-lecular markers of plasticity across wake and sleep.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

The evidence supports the occurrence of environmentally induced paternal epigenetic inheritance shaping the offspring phenotype in the absence of direct or indirect paternal care, and the empirical results clearly indicate that sperm epigenetics is one of the major actors mediating these paternal effects. However, sperm often make up only a small fraction of the male ejaculate in animals. Males also have a complex mixture of proteins, peptides, types of small RNAs, and cell-free DNA fragments in their seminal fluid. These molecules are in close contact with reproductive cells, tissues, organs, and other molecules of both males and females during reproduction. Moreover, their production and use are very sensitive to environmental conditions which makes them potential modulators of environmentally and developmentally induced paternal effects on the next generation(s). Although there is some intriguing evidence of seminal fluid-mediated paternal epigenetic effects, the underlying molecular mechanisms remain poorly defined. In this review, I discuss the current evidence regarding the association between seminal fluid and environmentally induced paternal effects, the possible trajectories, and the mechanisms in which seminal fluid can involve to mediate paternal epigenetic inheritance.

Phenotypic switching in cancer cells has been found to be present across tumor types. Recent studies on Glioblastoma report a remarkably common architecture of four well-defined phenotypes coexisting within high levels of intra-tumour genetic heterogeneity. Tumours grown from any cell type recapitulate the original phenotypic composition. Similar dynamics have been shown to occur in breast cancer, melanoma and likely across further cancer types. Given the adaptive potential of phenotypic switching (PHS) strategies, understanding how it drives tumour evolution and how to break down these architectures is a major priority. Here we model the ecological dynamics behind PHS. The model is able to reproduce experimental results, and specific conditions for cancer progression and clearance reveal novel features of plastic tumours and its direct consequences on therapy resistance. Following our results we discuss \textit{transition} therapy as a novel scheme to target not only combined cytotoxicity but also the rates of phenotypic switching.

One ambitious objective of Integrated Computational Materials Engineering (ICME) is to shorten the materials development cycle by using computational materials simulation techniques at different length scales. In this regard, the most important aspects are the prediction of the microstructural evolution during material processing and the understanding of the contributions of microstructural features to the mechanical response of the materials. One possible solution to such a challenge is to apply the Phase Field (PF) method because it can predict the microstructural evolution under the influence of different internal or external stimuli, including deformation. To accomplish this, it is necessary to take into account plasticity or, specifically, non-homogeneous plastic deformation, which is particularly important for investigating the size effects in materials emerging at the micron length scale. In this work, we present quasi-2D simulations of plastic deformation in a face centred cubic system in a finite strain formulation. Our model consists of dislocation-based strain gradient crystal plasticity implemented into a PF code. We apply this model to study the influence of grain size on the mechanical behavior of polycrystals, which includes dislocation storage and annihilation. Furthermore, the initial state of the material before deformation is also considered. The results show that a dislocation-based strain gradient crystal plasticity model can capture the Hall-Petch effect in many aspects. The model reproduced the correct functional dependence of the flow stress of the polycrystal on grain size without assigning any special properties to the grain boundaries. However, the predicted Hall-Petch coefficients are significantly smaller than those found typically in experiments. In any case, we found a good qualitative agreement between our findings and experimental results.

The development and generalization of Digital Volume Correlation (DVC) on X-ray computed tomography data highlight the issue of long term storage. The present paper proposes a new model-free method for pruning the DVC data. The size of the remaining sampled data can be user-defined, depending on the needs concerning storage space. The data pruning procedure is deeply linked to hyper-reduction techniques. The DVC data of a resin-bonded sand tested in uniaxial compression is used as an illustrating example. The relevance of the pruned data is tested afterwards for model calibration. A new Finite Element Model Updating (FEMU) technique coupled with an hybrid hyper-reduction method is used to successfully calibrate a constitutive model of the resin bonded sand with the pruned data only.

Major depressive disorder (MDD) is a common mental disorder, which results in seriously impaired condition in the patients and great global disability burden. In light of its quite diverse etiologies, comorbidity with many other diseases, and complex underlying pathology, it has been a great challenge to understand the physiological basis of MDD, which may be a complex of related diseases, rather than a single one. In addition to the partial understanding of MDD, the individual heterogeneities among patients may render the development of a universal treatment an elusive goal. But studying how each of currently available treatments affects the disease can generate useful information to stratify patients into different subtypes for individualized treatments. In this case report, we present the first report of repeated success of using meditation as the only treatment of MDD, compared to initial success but no remission with other conventional antidepressants on the same patient. We hypothesized that the short but continuous natural pain during one-hour meditation sittings has the therapeutic effect to treat depression in the case of this patient and potentially others with MDD. This special opportunity of eliminating tremendous heterogeneity among different individuals has enabled us to probe deeply into the potential mechanism of depression treatments and the complex physiology of depression itself, both of which have likely profound implications in the treatment of other MDD patients as well. More importantly, this case report helps us dissect one specific component of meditation for its long-known and well-established benefit against depression.

Floods are among the most serious natural disasters worldwide; they cause enormous crop losses every year and threaten world food security. There are many studies focused on flood impact assessments for administrative districts but fewer on postdisaster impact assessments for specific crops. Therefore, this study used remote sensing data, including the normalized difference vegetation index (NDVI), elevation data, slope data, and rainfall data, combined with crop growing season data to construct a crop flood damage assessment index (CFAI). First, an analytic hierarchy process (AHP) was used to assign weights to the impact factors; then, the weighted composite score method was used to calculate the CFAI; and finally, the impact was classified as slight, moderate, or severe based on the magnitude of the CFAI . This method was used for the Missouri River floods of 2019 in the U.S. Due to the lack of measured data, the disaster vegetation damage index (DVDI) was used to validate the results. The combined approach achieved a high degree of consistency in spatial distribution. The CFAI can respond well to the degree of crop impact after flooding, providing new ideas and reference standards for agriculture-related departments.

Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine level in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The pa-tients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n= 50), a tetrahydrobiopterin group (n= 44) and a group taking tetra-hydrobiopterin together with the diet (n= 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average €18801±15345 and was lowest in the diet group, then in the tetrahydrobiopterin group and highest in the tetrahydrobiopterin+diet group (p < 0.001). Out-of-pocket costs amounted to €1531±1173 per year, and indirect losses aver-aged €2125±1930 per year for all families. The economic loss was significantly lower in the fami-lies taking tetrahydrobiopterin than in the other groups (p=0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic harm to the state. Reim-bursing low-protein products and increasing the rate of patients eligible for financial allowances may reduce the economic harm to families.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

This paper discusses the theoretical and experimental correlations between fatigue and static strength statistical distributions. We use a two-parameter residual strength model that obeys the qualitative Strenght-Life Equal-Rank (SLERA) assumption for guidance. The modeling approach consists of recovering the model's parameters by best fitting the constant amplitude (CA) fatigue data at a given stress ratio, R, and the experimental Weibull parameters of the static strength distribution function. Once the model's parameters are fixed, its capabilities, potential, and limits are discussed by comparing its predictions with residual strength and fatigue data obtained at different stress ratios, R. Moreover, from a preliminary analysis, the theoretical extension of the model's capabilities to variable amplitude loadings is conceptualized. The application of Miner's rule is also discussed and compared with a new damage rule to analyze the fatigue responses under variable amplitude loadings.

Wildfires can be destructive to highway infrastructure. Despite the substantial number of wildfires experienced every year, research on the physical impacts of wildfire on highways has been understudied. This research examines historical and potential future highway physical damage from wildfires. To accomplish our research objectives, we examined three major areas related to physical harm to highways and the consequences of that damage – physical characteristics, roadway impacts, and traffic impacts. These categories were subsequently broken into additional metrics, the first being physical characteristics, which includes length of highway affected and reduced average daily traffic (RADT) impacts during the event. Roadway impacts were broken into the number of trees requiring removal (those that present a danger either standing or fallen), pavement damage (burning asphalt concrete), slope/rock scaling (loose hazard rocks/vegetation), and structural damage (guardrail, signs, and delineators). Traffic impacts included the need for traffic control, road closures required, and reduced annual average daily traffic (RAADT) impacts for the year. The physical characteristics on the three highways researched during the 2020 Oregon Labor Day wildfires (Beachie Creek, Archie Creek, and Holiday Farm) indicated less than 61% of the highways were affected. The highway impacts, which included damage from hazard trees, damage to various structures – guardrail, signs, and delineators as well as bridges, slope/rock scaling damage and pavement destruction – averaged 34% for the three highways, while the three of eight arterial highway routes studied in the Oregon Cascades saw a 21% reduction in AADT. Results from this study can be used not only to assess physical damage to highways from wildfires, but as a baseline for measuring and assessing potential future wildfire highway impacts.

This paper presents an approach to damage identification in beams by modal curvatures based on the use of beamforming algorithms. These processors have been successfully used in acoustics for the last thirty years to solve the inverse problems encountered in source recognition and image reconstruction, based on ultrasonic waves. In addition, beamformers apply to a broader range of problems in which the forward solutions are computable and measurable, especially regarding the field of structural vibrations, where the use of such estimators has not received attention to date. In this paper, modal curvatures will play the role of the replica vectors of the imaging field. By means of numerical studies and experimental tests on a steel beam, we motivate the choice of modal curvatures as observed quantities. Furthermore, we compare the performance of the Bartlett and minimum variance distortionless beamformers (MVDR) with an estimator based on the simple minimization of the difference between model and measured data. The results suggest that the application of the MVDR beamformer is highly effective, especially in cases of slight damage between two sensors. MVDR enabled both damage localization, and quantification.

The paper explores the potential of a low-cost advanced video-based technique for the assessment of structural damage induced to buildings by seismic loading. A low-cost high-speed video camera was utilized for motion magnification (MM) processing of footages of a two-story reinforced concrete frame building subjected to shaking table tests. The damage after seismic loading was estimated by analyzing the dynamic behavior (i.e. in terms of modal parameters) and the structural deformations of the building in the MM videos. The results by MM were compared for method validation to damage assessment obtained by the analyses of conventional accelerometers and high-precision optical markers tracked by a passive 3D motion capture system. Also, 3D laser scanning to obtain an accurate survey of the building geometry before and after the seismic tests was carried out. In particular, accelerometers were also processed and analyzed by using several stationary and non-stationary techniques with the aim to analyze the linear behavior of the undamaged structure and the nonlinear structural behavior during damaging shaking table tests. The proposed MM-based procedure provided accurate estimate of the main modal frequency and the damage location through the analysis of modal shapes, which were confirmed by advanced analyses of accelerometric data.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Critical infrastructures are those that are essential. For this type of infrastructure, it is necessary to implement analytical methodologies that will allow us to quickly obtain the susceptibility or resilience and possible damage generated in extreme precipitation episodes, through a holistic perspective in which the factors linked to hydrological risk intervene. In particular, urban hydraulic infrastructures are analyzed considering the degree of criticality, defined as the number of interactions on the different activities of the population. For this purpose, a hydrological risk analysis methodology is required. This methodology is focused on an integral approach of the system indicators to be analyzed and linked to the hydrological threat. This work proposes to delimit and analyze those factors that involve risk using an analytical expression. This model will estimate the damage to these infrastructures breaking down the factors involved in the risk equation and analyzing their variability according to the intrinsic characteristics linked to them as well as the interaction with external factors.

Magnetorheological processing was applied to polish the working surfaces of the ZnGeP2 single crystal, in which a non-aqueous liquid with magnetic particles of carbonyl iron with the addition of nanodiamonds was used. Samples of a single crystal ZnGeP2 with an angstrom level of surface roughness were received. the use of MRP has allowed more accurately characterizing possible structural defects that have emerged on the surface of a single crystal and have a size of ~ 0.5-1.5 μm. the LIDT value at the indicated or-ders of magnitude of the surface roughness parameters is determined not by the quality of polishing, but by the number of point depressions caused by physical limitations of the structural configuration of the crystal volume. These results are in good agreement with the assumption made about a significant effect of the concentration of dislocations in a ZnGeP2 crystal on LIDT.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis but little is known about the molecular mechanisms involved. The recently developed HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV) develop a liver pathology very similar to the human disease, and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression HDV antigens (HDAgs), characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and the L-HDAg is essential for HDV infectious particle production. We have also found that the lack of L-HDAg resulted in the increase of of S-HDAg expression levels and the exacerbation of liver damage which is T cell independent but is associated with an increment in liver inflammation. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only the S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

To quantify damage to reinforced concrete (RC) column members after an earthquake, an engineer needs to know the maximum applied force that was generated by the earthquake. Therefore, in this work, piezoceramic transducers are used to detect the applied force on an RC column member under dynamic loading. To investigate the use of post-embedded piezoceramic sensors in detecting the force that is applied to RC columns, eight full-size RC column specimens with various failure modes are tested under specific earthquake loadings. Post-embedded piezoceramic sensors are installed at a range of depths (70-80 mm) beneath the surface of a column specimen to examine the relationship between the signals that are obtained from them and the force applied by the dynamic actuator. The signals that are generated by the post-embedded piezoceramic sensors, which correlate with the applied force, are presented. These results indicate that the post-embedded piezoceramic sensors have great potential as tools for measuring the maximum applied force on an RC column in an earthquake. Restated, signals that are obtained from post-embedded piezoceramic sensors on an RC column in an earthquake can be used to determine the applied force and corresponding damage or residual seismic capacity.

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

The use of fluoride (F^-) for decreasing the prevalence and incidence of tooth decay was the greatest worldwide preventive public health measure of the 20th century. There have been controversial reports about the benefits of the use of F^-, because in small amounts it helps prevent dental caries, but in high concentrations it can be potentially toxic and harmful to dental and systemic health. Since the mid-20th century, F^- has been studied by toxicologists, looking at its deleterious effects in human populations. During the last decade, the interest on the undesirable effects has resurfaced because of the knowledge that it interacts with the cellular system, even in low doses, with a very small safety margin. Acute ingestion of toxic amounts of fluoride can cause corrosive gastric mucosa injury. Also respiratory effects such as bleeding, pulmonary edema, tracheostomy and shortness of breath, have been observed in individuals who inhale hydrogen fluoride. Some researchers had shown that F^- is an oxidizing agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins, can altered the intracellular redox equilibrium, lipid peroxidation, as well as, alteration in the gene expression and apoptosis induction. The primary purpose of this review is to examine findings of the action of inorganic F^-, and an overview of hard and soft tissue disturbances, known as fluorosis. The goal of this review is to enhance understanding of the mechanisms by which F^- affects cells with an emphasis on human tissue-specific events.

The purpose of the present study was to examine if 14 days of supplementation with a pine bark extract leading up to and following an exercise test would increase performance and reduce biomarkers associated with muscle damage, inflammation and oxidative stress. The study used a double-blind, placebo controlled, cross-over design. Participants ingested either 800mg pine bark extract or placebo for 14 days prior to the first exercise trial and for 2 days post-exercise. On the exercise day, participants submitted a pre-exercise blood sample, then completed a VO₂ peak test until volitional failure. A post-blood sample was collected 1 hour after completion of exercise. Participants returned at 24 & 48 hours after the exercise testing for measures of muscle pain in the lower body using an algometer. Participants then had a 7-day washout period before beginning to crossing over to the alternate treatment. Analysis via ordinal regression demonstrated a significant difference in oxidative stress in the pine bark extract group compared to placebo (ChiSq = 2.63; p = 0.05). The pine bark extract was effective at affording protection from oxidative stress post exercise. Further work should be undertaken to evaluate the findings with other exercise modes or in participants with known metabolic syndrome.

Based on PVDF (piezoelectric sensing techniques), this paper attempts to study the propagation law of shock waves in brittle materials during the process of three-wavelength laser irradiation of polysilicon, and discusses the formation mechanism of thermal shock failure. The experimental results show that the vapor pressure effect and the plasma pressure effect in the process of pulsed laser irradiation lead to the splashing of high temperature and high density melt. With the decrease of the laser wavelength, the laser breakdown threshold decreases and the shock wave is weakened. Because of pressure effect of the laser shock, the brittle fracture zone is at the edge of the irradiated area. The surface tension gradient and surface shear wave caused by the surface wave are the result of coherent coupling between optical and thermodynamics. The average propagation velocity of laser shock wave in polysilicon is 8.47×103m/s, and the experiment has reached the conclusion that the laser shock wave pressure peak exponentially distributes attenuation in the polysilicon.

The 1060 aluminium alloy is widely applied to electronic industry, construction area, aerospace field, traffic engineering, decoration and consumption goods market for its good chemical, physical and mechanical properties. In general, excellent processing property is necessary and important for manufacturing of complicated panels. In this paper, a special 2D ultrasonic vibration incremental forming method is designed to improve its plasticity and mechanical properties. Three kind of processing methods including traditional single point incremental forming, longitudinal ultrasonic vibration incremental forming and 2D ultrasonic vibration incremental forming are conducted for flexible manufacture of conical parts of 1060 aluminium alloy sheet. Then micro-hardness tests, residual stress tests and scanning electron microscopy tests are carried out to probe its revolution of micro-structure and mechanical properties and to analysis the effects of different types of ultrasonic vibration on plasticity and fracture characteristic of 1060 aluminium alloy. It is proved that 2D ultrasonic vibration is facilitated to improvement of plasticity and surface qualities of 1060 aluminium alloy than the other two processing methods. So, the novel 2D ultrasonic vibration incremental forming possesses substantial application values on flexible and rapid manufacturing of complicated thin-walled component of aluminium alloy.

Precipitates are the primary source of strength for the Al-Mg-Si alloy. Aluminum alloy in the peak-aged state mainly contain β'' and β' precipitates. In the past, most of the literature only considered the strengthening effect of β''. Here we develop a single crystal intensity model including both precipitate enhancement effects for the first time. This model was subsequently implemented into a crystal plastic finite element method to model the uniaxial tensile process of a polycrystalline aggregate model of Al-Mg-Si alloy. The simulation results for uniaxial stretching are in good agreement with the experimental results, confirming that the constitutive parameters used for the single crystal strength model with two precipitates are based on realistic physical implications. Furthermore, by comparing the uniaxial tensile simulation results of a peak-aged alloy considering the actual precipitated phase composition of the alloy with those assuming that the precipitated phase is only the β'' phase, the predicted tensile strength of the former is around 5.65% lower than that of the latter, suggesting that the two kinds of precipitation should be considered separately when simulating the mechanical response of Al-Mg-Si alloy. It is highly expected that the present simulation strategy is not limited to the Al-Mg-Si alloys, and it can be equally applied to the other age-enhanced alloys.

Background: As cancer progresses, cells acquire traits that allow them to disperse and disseminate to distant locations in the body – a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can manifest either as single cells or clusters of cells (i.e., CTC clusters), with the latter being the most aggressive. The increased metastatic potential of CTC clusters is generally associated with cooperative group benefits in terms of survival, such as increased resistance to shear stress, anoikis, immune attacks and drugs. However, the adoption of a group phenotype poses a challenge when exiting the vasculature (extravasation) as the large size can hinder the passage through vessel walls. Despite their significant role in the metastatic process, the mechanisms through which CTC clusters extravasate remain largely unknown. Based on the observed in vivo association between CTC clusters and platelets, we hypothesized that cancer cells take advantage of the platelet-derived Transforming Growth Factor Beta 1 (TGF-β1) – a signalling factor that has been widely implicated in many aspects of cancer, to facilitate their own dissemination. To address this possibility, we evaluated the effect of exogenous TGF-β1 on an experimentally evolved non-small lung cancer cell line that we previously developed and used to investigate the biology of CTC clusters. Results: We found that exogenous TGF-β1 induced the dissociation of clusters into adherent single cells. Once adhered, cells released their own TGF-β1 and were able to individually migrate and invade in the absence of exogenous TGF-β1. Based on these findings we developed a model that involves a TGF-β1-mediated plastic switch between a cooperative phenotype and a single-celled stage that enables the extravasation of CTC clusters. Conclusions: This model allows for the possibility that therapies can be developed against TGF-β1 signalling components and/or TGF-β1 target genes to suppress the metastatic potential of CTC clusters. Considering the negative impact that metastasis has on cancer prognosis and the lack of therapies against this process, interfering with the ability of CTC clusters to switch between cooperative and individual behaviours could provide new strategies to improve patient survival.

Disruptive selection arises when extreme phenotypes have a fitness advantage compared to more intermediate phenotypes. Theory and evidence suggest that intraspecific resource competition is a key driver of disruptive selection. However, while competition can be indirect (exploitative) or direct (interference), the role of interference competition in disruptive selection has not been tested, and most models of disruptive selection assume exploitative competition. We experimentally investigated whether the type of competition affects the outcome of competitive interactions using a system where disruptive selection is common: Mexican spadefoot toads (Spea multiplicata). Spea tadpoles develop into alternative resource-use phenotypes: carnivores, which consume fairy shrimp and other tadpoles, and omnivores, which feed on algae and detritus. Tadpoles intermediate in phenotype have low fitness when competition is intense, as they are outcompeted by the specialized tadpoles. Our experiments revealed that the presence of carnivores significantly decreased foraging behavior in intermediate tadpoles, and that intermediate tadpoles had significantly lower growth rates in interference competition treatments with carnivores but not with omnivores. Interference competition may therefore be important in driving disruptive selection. As carnivore tadpoles are also cannibalistic, the ‘fear’ effect may have a greater impact on intermediate tadpoles than exploitative competition alone, similarly to non-consumptive effects in predator-prey or intraguild relationships.

The great pipefish Syngnathus acus is one of the most representative European syngnathid, being highly associated with seagrass and macroalgal beds. Surprisingly, the ecology of this ovoviviparous marine fish has received scanty attention. The population inhabiting three sites on Cíes Archipelago (Atlantic Islands National Park, NW Spain) was monitored in 2017-2018 for spatial and temporal changes in abundances, reproduction traits, trophic niche occupancy and dietary regimes across reproduction states through an isotopic (δ13C and δ15N) approach. Abundances were highly variable across seasons and sites, decreasing significantly from mid-autumn. The population consisted almost exclusively of large adults that migrate by the end of the breeding season, which extended from mid-spring to summer. Operational sex ratios suggest that the species is sex-role reversed. S. acus is a secondary consumer (Trophic position= 3.36 ± 0.05) preferring amphipods but displaying annual and seasonal dietary plasticity. Mature fish were less selective than immatures (especially females) with a higher preference for amphipods (36-68%) in the former. The second most preferred prey were carideans, copepods or isopods, depending on the year and reproduction state. Overall, the wider trophic niches in females and immature specimens compared to males and mature fish would indicate a higher variability in both the use of prey resources and/or their origin. The present study highlights the trophic plasticity and unique features of S. acus population in Cíes Archipelago, especially regarding the outstanding size of the fish and the exceptional occurrence of breeders.

Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994–2004) – when the two-neurogenic-niche concept in humans was consolidated – and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

In order to alleviate the problems regarding conventional damping modeling techniques in nonlinear structural simulations, using concentrated plasticity formulation including rotational end springs with no damping plus middle elastic parts with modified assigned damping has recently been proposed. However, a proper selection for springs’ stiffness is a source of contention. In this paper, the effect of choosing different ratios for springs’ rotational stiffness to the elastic part of the elements on the seismic performance of RC moment frames was investigated. Incremental Dynamic Analysis (IDA) was performed and the derived responses were used for seismic performance assessment methodology. The results demonstrate that using flexible springs may lead to a greatly conservative estimation of collapse capacity, annual losses, and repair costs compared to a rigid one. Due to lack of experimental data, it is not possible to certainly assert the most appropriate ratio. However, such variation in the seismic performance of a building model with different stiffness modification necessitates more investigation on this modeling strategy.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

We present a high-throughput nanoindentation study of in-situ bending effects on incipient plastic deformation behavior of polycrystalline and single-crystalline pure aluminum and pure copper at ultra-nano depths (<200nm). We find that hardness displays a statistically inverse dependence on in-plane stress for indentation depths smaller than 10nm, and the dependence disappears for larger indentation depths. In addition, plastic noise in the nanoindentation force and displacement displays statistically robust noise features, independently of applied stresses. Our experimental results suggest the existence of a regime in FCC crystals where ultra-nano hardness is sensitive to residual applied stresses, but plasticity pop-in noise is insensitive to it.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Advanced machine learning algorithms, have the potential to be successfully applied to many areas of system modelling. In the present study the capability of ten machine learning algorithms in predicting the structural damage of an 8-storey reinforced concrete frame building subjected to single and successive ground motions is examined. From this point of view, the initial damage state of the structural system, as well as 16 well known ground motion intensity measures are adopted as the features of the machine-learning algorithms that aim to predict the structural damage after each seismic event. The structural analyses are performed considering both real and artificial mainshock–aftershock sequences, while the structural damage is expressed in terms of two overall damage indices. The comparative study results in the most efficient damage index, as well as the most promising machine learning algorithm in predicting the structural response of a reinforced concrete building under single or multiple seismic events. Finally, the configured methodology deployed in a user-friendly web-application.

Sirtuins (SIRTs) are a family of evolutionarily conserved enzymes, and the aim of this study was to disclose/re-annotate uncertain paralogs in gilthead sea bream, expanding from seven to ten the repertoire of Sirts in this Perciform fish. Such gene expansion revealed up to three copies of sirt3 (sirt3.1a/sirt3.1b/sirt3.2) and two of sirt5 (sirt5a/sirt5b). Phylogenetic and synteny attempts disclosed the duplication of SIRT3/Sirt3 branch as a process shaped by the 2R whole genome duplication (WGD) at the early vertebrate evolution, with still vestiges in all living fish, and some Sarcopterygii. In gilthead sea bream and other Percomorphaceae, this duplication was accompanied by short segmental duplications of sirt3.1 (clustered to the mammalian SIRT3 ortholog), making a conserved tandem-duplicated synteny block (psmd13-sirt3.1a/b-drd4-cdhr5-ctsd). Conversely, the expansion of the Sirt5 branch was shaped by the 3R WGD as a specific event of the teleost fish lineage. Intriguingly, gene expression profiling across tissues and developmental stages highlighted a conserved high expression of sirt3.1 and sirt5a in skeletal muscle, while the duplicated sirt3.2 and sirt5b displayed an overall muscle suppression of transcriptional activity, and an enhanced expression on immune-relevant tissues and gills, respectively. Altogether offers new insights about the function, regulation, and timing of Sirt expansion.

This paper aims to quantify the influence of hydrogen embrittlement on Wierzbicki and Xue (W-X) model parameters. This model has 4 parameters which have been obtained by tensile tests on smooth specimens, tensile notch specimens, single notch tensile specimens (SENT) and pure shear specimens. Hydrogen embrittlement has been obtained by electrolytic method. Application of the (W-X) model has been done to get the local resistance used to predict failure by the Volumetric Method (VM). An example is given for the case of an embedded pipe submitted to service pressure and lateral seismic displacement. The effect of this displacement is then assimilated to the shearing of the straight section of the pipe. The pipe shows a corrosion defect considered a semi-elliptical crack. The influence of hydrogen embrittlement on local strain resistance and safety factors is discussed.

Working memory (WM) is a brain system for short-term storage and manipulation of information and plays an important role in complex cognitive tasks. In the synaptic theory of WM memorized elements are stored in the form of short-term potentiated connections in a sample population of neurons. In this paper, we show that such populations can be formed due to the mechanisms of spike-timing-dependent plasticity (STDP) – the phase dependence associated with the ratio of the pulse times of the interacting neurons. We propose a WM model considering two types of plasticity: short-term plasticity and STDP. We have shown formation of neuronal clusters encoding items in the WM model, that can be formed by external stimulation of a group of neurons due to the mechanisms of STDP and hold and reactivated by short-term plasticity mechanisms. The dynamic formation of neuronal clusters instead of pre-formed clusters gives additional flexibility to the model.

This study employs a high-fidelity numerical framework to determine the plastic material flow patterns and temperature distributions that lead to void formation during friction stir welding (FSW), and to relate the void morphologies to the underlying alloy material properties and process conditions. Three aluminum alloys, viz., 6061-T6, 7075-T6, and 5053-H18 were investigated under varying traverse speeds. The choice of aluminum alloys enables investigation of a wide range of thermal and mechanical properties. The numerical simulations were validated using experimental observations of void morphologies in these three alloys. Temperatures, plastic strain rates, and material flow patterns are considered. The key results from this study are: (1) The predicted stir zone and void morphology are in good agreement with the experimental observations, (2) The temperature and plastic strain-rate maps in the steady-state process conditions show a strong dependency on the alloy type and traverse speeds, (3) The material velocity contours provide a good insight into the material flow in the stir zone for the FSW process conditions that result in voids as well as those that do not result in voids. The numerical model and the ensuing parametric studies presented in this work provide a framework for understanding material flow under different process conditions in aluminum alloys, and potentially in other alloys. Furthermore, the utility of the numerical model for making quantitative predictions and investigating different process parameters to reduce void formation is demonstrated.

Background: Drought, N deficiency and herbivory are considered the most important stressors caused by climate change in the agro- and eco-systems and varied in space and time shaping a highly dynamic and heterogeneous stressful environments. This study aims to evaluate the to-mato morpho-physiological and metabolic responses to combined abiotic and herbivory at dif-ferent within-plant spatial levels and temporal scales. Methods: Leaf-level morphological, gas exchange traits and VOC profiles were measured in to-mato plants exposed to N deficiency and drought, T. absoluta larvae and their combination. Ad-ditive, synergistic or antagonistic effects of the single stress when combined were also evaluat-ed. Morpho-physiological traits and VOC profile were also measured on leaves located at three different positions along the shoot axes. Results: The combination of the abiotic and biotic stress has been more harmful than single stress with antagonistic and synergistic but non-additive effects for the morpho-physiological and VOC tomato responses, respectively. Combined stress also determined a high within-plant phenotypic plasticity of the morpho-physiological responses. Conclusions: These results suggest that the combined stress in tomato determined a “new stress state” and a higher within-plant phenotypic plasticity which could permit an efficient use of the growth and defence resources in the heterogeneous and multiple stressful environmental condi-tions.

Salvia ceratophylloides (Ard.) is an endemic, rare, threatened plant species recently rediscovered in very few individuals in two different sites of South Italy. The study of within-plant variation more than among-plant one is fundamental to understand the plant adaptation to the local conditions, especially in rare species, and consequently to preserve plant biodiversity. Here, we reported the variation of the morpho-ecophysiological and metabolic traits between the sessile and petiolate leaf of S. ceratophylloides plants in two different sites for understanding the adaptation strategies for surviving in these habitats. The S. ceratophylloides individuals exhibited different net photosynthetic rate, maximum quantum yield, light intensity for the saturation of the photosynthetic machinery, stomatal conductance, transpiration rate, leaf area, fractal dimension and some VOCs between the different leaf types. This within-plant morpho-physiological and metabolic variation was depended on the site. These results provide empirical evidence of sharply within-plant variation of the morpho-physiological traits and VOCs profiles in S. ceratophylloides which could be because of adaptation to the local conditions.

Previously we demonstrated, in rats, that the treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or vehicle (V), for five days. At 1 dpi (days after injury), 5 rats received daily injections (4 days) of bromodeoxyuridine and were sacrificed. The other 15 rats (n = 5 / group) underwent treatment and rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent of GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

Zirconia-reinforced lithium silicate (ZLS) is utilized as a material for prosthetic tooth crowns, offering enhanced strength compared to other dental glass-ceramics. In this study, we investigate a commercial ZLS material, provided in a fully crystallized form. We examine the effects of an optional post-processing heat treatment on micro-contact damage using controlled indentation tests simulating the primary modes of contact during chewing: axial and sliding. Our findings indicate that the heat treatment does not affect mechanical properties such as the elastic modulus, hardness and indentation fracture toughness. However, it does enhance the resistance to contact damage by fracture and chipping in both axial and sliding modes, as well as the resistance to crack initiation measured from sliding tests. This improvement is attributed to the refinement of the flaw population achieved through the heat treatment. The results are analysed within the framework of contact and fracture mechanics, and the implications for prosthetic dentistry are briefly discussed.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

(1) Background: Ultra-endurance exercise involves a high physical impact, resulting in muscle damage, inflammatory response and production of free radicals that alter the body's oxidative state. Supplementation with antioxidants, such as beetroot, may improve recovery in ultra-endurance runners. The aim of this study was to determine whether there is a correlation between the beetroot intake and the recovery of serum oxidative status, inflammatory response and muscle damage parameters after an ultra-endurance race. (2) Methods: An observational and longitudinal study was conducted by means of surveys and blood samples collected from 32 runners during the IX Penyagolosa Trails CSP® race and the two following days. The variables C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase (CK), the activity of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the oxidative damage markers malondialdehyde (MDA), carbonyl groups (CG) and loss of muscle strength using the Squat Jump test (SJ) were analyzed to discriminate whether beetroot consumption can modulate the recovery of ultra-trail runners. (3) Results: Significant differences were observed between runners who ingested beetroot and those who did not, in terms of oxidative status, specifically in serum GPx activity at 24 and 48 hours, muscle damage variables CK and LDH and in SJ test at the finish line. Therefore, the intake of supplements containing beetroot positively influences the recovery of serum oxidative status and muscle damage after ultra-endurance running.